Metastasis Markers

A unique and clinically decisive feature of cancer cells is their capability to disseminate from their point of origin invading secondary and distal tissue sites, a set of events known as metastasis.

The metastasis cascade refers to the sequential events enabling cancer cells to detach from each other in situ and escape from the primary tumor site. The final destination of metastatic cells is non-random and depends on both tissue vascularization and on the expression of particular homing proteins in the respective cell surfaces.

Matrix metalloproteases (MMPs)

Metastatic tumor cells lose their adhesive properties and contact with the basement membrane. This process depends for instance, on the expression of matrix metalloproteases (MMPs). MMPs degrade the basement membrane, allowing cells to disseminate, then reach their distal destinations via vascular routes (blood and lymph vessels). They finally converge the formation of clinically detectable secondary tumors in distal organs - metastases.

Epithelial-to-Mesenchymal-Transition (EMT)

When metastatic cells exit from the primary site and during dissemination, they are reprogrammed into a mesenchymal phenotype through the Epithelial-to-Mesenchymal-Transition (EMT). Here, cancers of epithelial origin acquire molecular signatures usually associated with “stem cell-like” phenotype. This includes for instance induction of TGF-beta, transcription factors Snail1- and -2, Twist, as well as the intermediate filament protein vimentin.

Learn more about the Epithelial-to-Mesenchymal (EMT) transition, and explore antibodies targeting EMT markers.

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Histopathological analysis of metastatic tumor cells

A histopathological analysis may enable the distinction of the invading tumor cells from the normal local tissue. Sometimes, the presence of invading metastases can be revealed by the differences in size and nuclear morphology (degree of pleomorphism) of the tumor cells versus the normal surrounding tissue. To that end, conventional Hematoxylin and Eosin (H&E) staining can be used.

However, to define the origin of the metastatic tumor cells using only conventional histopathology can be challenging. Therefore, specific phenotypic IHC-markers like cytokeratins KRT7 and KRT20 can be used, often as a panel of different markers.